Relations between Effects and Structure of Small Bicyclic Molecules on the Complex Model System Saccharomyces cerevisiae

The development of compounds able to modify biological functions largely took advantage of parallel synthesis to generate a broad chemical variance of compounds to be tested for the desired effect(s). The budding yeast Saccharomyces cerevisiae is a model for pharmacological studies since a long time as it represents a relatively simple system to explore the relations among chemical variance and bioactivity. To identify relations between the chemical features of the molecules and their activity, we delved into the effects of a library of small compounds on the viability of a set of S. cerevisiae strains. Thanks to the high degree of chemical diversity of the tested compounds and to the measured effect on the yeast growth rate, we were able to scale-down the chemical library and to gain information on the most effective structures at the substituent level. Our results represent a valuable source for the selection, rational design, and optimization of bioactive compounds

Diffusion of individual birds in starling flocks

Flocking is a paradigmatic example of collective animal behaviour, where decentralized interaction rules give rise to a globally ordered state. In the emergence of order out of self-organization we find similarities between biological systems, as bird flocks, and some physical systems, as ferromagnets. In both cases, the tendency of individuals to align to their neighbours gives rise to a polarized state. There is, however, one crucial difference: the interaction network within an animal group is not necessarily fixed in time, as each individual moves and may change its neighbours. Therefore, the dynamical interaction mechanism in biological and physical system can be quite different, not only due to the gross disparity in the complexity of the individual entities, but also because of the potential role of inter-individual motion. To assess the relevance of this mechanism it is necessary to gain quantitative experimental information about how much individuals move with respect to each other within the group. Here, by using data from field observations on starlings, we study the diffusion properties of individual birds within a flock and investigate the effect of diffusion on the dynamics of the interaction network. We find that birds diffuse faster than Brownian particles (superdiffusion) and in a strongly anisotropic way. We also find that neighbours change in time exclusively as a consequence of diffusion, so that no specific mechanism to keep one's neighbours seems to be enforced. Finally, we study the diffusion properties of birds at the border of the flock. We find that these individuals remain on the border significantly longer than what would be expected on the basis of a purely diffusional model, suggesting that there is a sort barrier a bird must cross to make the transition from border to interior of the flock.Comment: 22 pages, 10 figure

Kineococcus radiotolerans Dps forms a heteronuclear Mn-Fe ferroxidase center that may explain the Mn-dependent protection against oxidative stress

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Linear electronics for Si-detectors and its energy calibration for use in heavy ion experiments

Abstract The design and implementation of linear electronics based on small-size, low-power charge preamplifiers and shaping amplifiers, used in connection with Si-detector telescopes employed in heavy ion experiments, are presented. Bench tests and "under beam" performances are discussed. In particular, the energy calibration and the linearity test of the overall system (Si-detector and linear and digital conversion electronics) has been performed with a procedure which avoids the pulse height defect problems connected with the detection of heavy ions. The procedure, basically, consists of using bursts of MeV protons, releasing up to GeV energies inside the detector, with low ionization density

Group 1 ITI Consensus Report: The role of bone dimensions and soft tissue augmentation procedures on the stability of clinical, radiographic, and patient-reported outcomes of implant treatment.

OBJECTIVES The aims of Working Group 1 were to address the role (i) of the buccolingual bone dimensions after implant placement in healed alveolar ridge sites on the occurrence of biologic and aesthetic complications, and (ii) of soft tissue augmentation (STA) on the stability of clinical, radiographic, and patient-related outcomes of implant treatments. MATERIALS AND METHODS Two systematic reviews were prepared in advance of the Consensus Conference and were discussed among the participants of Group 1. Consensus statements, clinical recommendations, recommendations for future research, and reflections on patient perspectives were based on structured group discussions until consensus was reached among the entire group of experts. The statements were then presented and accepted following further discussion and modifications as required by the plenary. RESULTS Dimensional changes of the alveolar ridge occurred after implant placement in healed sites, and a reduction in buccal bone wall thickness (BBW) of 0.3 to 1.8 mm was observed. In healed sites with a BBW of <1.5 mm after implant placement, increased vertical bone loss, and less favorable clinical and radiographic outcomes were demonstrated. Implants with buccal dehiscence defects undergoing simultaneous guided bone regeneration, showed less vertical bone loss, and more favorable clinical and radiographic outcomes, compared to non-augmented dehiscence defects during initial healing. At healthy single implant sites, probing depths, bleeding and plaque scores, and interproximal bone levels evaluated at 1 year, remained stable for up to 5 years, with or without STA. When single implant sites were augmented with connective tissue grafts, either for soft tissue phenotype modification or buccal soft tissue dehiscence, stable levels of the soft tissue margin, and stable or even increased soft tissue thickness and/or width of keratinized mucosa could be observed from 1 to 5 years. In contrast, non-augmented sites were more prone to show apical migration of the soft tissue margin in the long-term. Favorable aesthetic and patient-reported outcomes after STA were documented to be stable from 1 to 5 years. CONCLUSIONS It is concluded that dimensional changes of the alveolar ridge occur after implant placement in healed sites and that sites with a thin BBW after implant placement are prone to exhibit less favorable clinical and radiographic outcomes. In addition, it is concluded that STA can provide stable clinical, radiographic, aesthetic, and patient-reported outcomes in the medium and long-term

Fiasco: a multidetector optimized for semiperipheral heavy ion collisions at Fermi energies

The Fiasco multidetector is a low-threshold apparatus, optimized for the investigation of peripheral to semi-central collisions in heavy ion reactions at Fermi energies. It consists of three types of detectors. The first detector layer is a shell of 24 position-sensitive Parallel Plate Avalanche Detectors (PPADs), covering about 70% of the forward hemisphere, which measure the velocity vectors of the heavy ðZ\10Þ reaction products. Below and around the grazing angle, behind the most forward PPADs, there are 96 DE–E silicon telescopes (with thickness of 200 and 500 mm; respectively); they are mainly used to measure the energy of the projectile-like fragment and to identify its charge and, via the time-of-flight of the PPADs, also its mass. Finally, behind most of the PPADs there are 158 (or 182, depending on the configuration) scintillation detectors, mostly of the phoswich type, which cover 25–30% of the forward hemisphere; they identify both light charged particles ðZ ¼ 1; 2Þ and intermediate mass fragments ð3pZt20Þ; measuring also their time-of-flight. r 2003 Elsevier B.V. All rights reserved

P1245 Polymorphic Variants of HSD3B1 Gene Confer Different Outcome in Specific Subgroups of Patients Infected With SARS-CoV-2

Introduction: Severe respiratory syndrome coronavirus 2 (SARS-CoV-2) uses the androgen receptor (AR), through ACE2 receptor and TMPRSS2, to enter nasal and upper airways epithelial cells. Genetic analyses revealed that HSD3B1 P1245C polymorphic variant increases dihydrotestosterone production and upregulation of TMPRSS2 with respect to P1245A variant, thus possibly influencing SARS-CoV-2 infection. Our aim was to characterize the HSD3B1 polymorphism status and its potential association with clinical outcomes in hospitalized patients with COVID-19 in Southern Switzerland. Materials and Methods: The cohort included 400 patients hospitalized for COVID-19 during the first wave between February and May 2020 in two different hospitals of Canton Ticino. Genomic DNA was extracted from formalin-fixed paraffin-embedded tissue blocks, and HSD3B1 gene polymorphism was evaluated by Sanger sequencing. Statistical associations were verified using different test. Results: HSD3B1 polymorphic variants were not associated with a single classical factor related to worse clinical prognosis in hospitalized patients with SARS-CoV-2. However, in specific subgroups, HSD3B1 variants played a clinical role: intensive care unit admission was more probable in patients with P1245C diabetes compared with P1245A individuals without this comorbidity and death was more associated with hypertensive P1245A>C cases than patients with P1245A diabetes without hypertension. Discussion: This is the first study showing that HSD3B1 gene status may influence the severity of SARS-CoV-2 infection. If confirmed, our results could lead to the introduction of HSD3B1 gene status analysis in patients infected with SARS-CoV-2 to predict clinical outcome. Keywords: HSD3B1 gene polymorphism; Likelihood-ratio tests; SARS-CoV-2; androgen receptor; direct sequencing